An unidentified mechanism tightly links changes in skeletal muscle vascular resistance to changes in oxidative metabolism during exercise. It appears that this mechanism dominates control of skeletal muscle vascular resistance under many conditions. Previous studies have ruled out certain vasodilator mechanisms such as lactic acid production and increased tissue osmolarity, but do not rule out a role for arterial wall pO2, potassium ion (K positive), adenosine, and/or inorganic phosphate. The proposed experiments are designed to distinguish among these alternatives by comparing the time dependent behavior (dynamics) of these local chemical alterations to those of oxygen consumption and vascular resistance during various time varying exercise patterns. Other experiments, involving, e.g. dietary K ion depletion, are designed to determine the effect of elimination of a particular mechanism on vascular resistance dynamics. We will also attempt to elucidate the mechanism of prolonged vasodilation following fatiguing exercise. Preliminary studies indicate that potassium ion, lactic acid, and osmolarity or factors closely related to oxidative metabolism cannot be involved. We have designed experiments to determine whether histamine or prostaglandins are involved in the control of this prolonged vasodilation. We will also determine whether adenosine or inorganic phosphate release is "uncoupled" from oxygen consumption during fatiguing exercise, and thus could be causing the prolonged vasodilation. Emphasis on the dynamics of vascular resistance and the local chemical events associated with exercise is proposed because such an approach should allow us to separate phasic from steady vascular control mechanisms and to uncover mechanisms which might be partially or totally redundant.